Factor IX dalcinonacog alfa
The leading recombinant human Factor IX on the market for treating acute bleeding episodes in individuals with hemophilia B is delivered intravenously due to its short half-life and is therefore not ideal for prophylactic treatment. Extended half-life agents used for prophylaxis also require intravenous dosing and have a prolonged period of low activity levels that increase the risk of spontaneous bleeding before the next dose is given prophylactically. Catalyst created an improved and potent Factor IX, dalcinonacog alfa, or DalcA, for the potential subcutaneous prophylactic treatment of hemophilia B. Dalcinonacog alfa has shown significantly higher potency in preclinical and early clinical studies compared with other Factor IX products on the market and in development.
Factor IX dalcinonacog alfa Phase 2b study in individuals with severe hemophilia B – open and enrolling
The subcutaneous Phase 2b study (NCT03995784) in individuals with severe hemophilia B is an open-label trial evaluating the ability of dalcinonacog alfa to maintain steady-state Factor IX levels above 12% in individuals with severe hemophilia B. The trial will enroll up to six subjects, who will receive a single intravenous dose, followed by daily subcutaneous doses of dalcinonacog alfa for 28 days. Pharmacokinetics, pharmacodynamics, safety, and tolerability of daily subcutaneous dosing and anti-drug antibody formation will also be monitored.
Factor IX dalcinonacog alfa Phase 1/2 proof-of-concept study in individuals with severe hemophilia B - complete
We have completed a Phase 1/2 trial (NCT03186677) that evaluated the safety and efficacy of daily subcutaneous administration of DalcA in individuals with severe hemophilia B. The study objective was to assess the ability of DalcA to increase trough Factor IX activity from approximately 1% to 12%, essentially converting patients from severe to mild hemophilia levels. The data demonstrated that DalcA was highly efficacious for the treatment of hemophilia B and achieved protective Factor IX activity levels between ~12-30%, corresponding to a reduced chance of spontaneous joint bleeds. Two subjects developed neutralizing antibodies (nAbs) to DalcA (one transient low-titer) that did not cross react with wild type FIX and, therefore, are not be referred to as inhibitors. The patients were able to successfully resume use of their prior FIX therapy. In 2018, a comprehensive investigation concluded that the immunogenic potential of DalcA was low, similar to that of commercial Factor IX products, and that drug product quality was also comparable to commercial Factor IX products. Based on the results of the evaluation and discussions with clinicians and regulatory experts, we are continuing development of DalcA and recently initiated a Phase 2b trial to assess the safety and efficacy of 28 days of daily subcutaneous dosing in six subjects (NCT03995784).